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Novel Variant Identified in the Enhancer Region of Host Transcription Factor, BRN3A, is a Significant Risk Factor for HPV-Induced Uterine Cervix Cancer
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Anand Prakash1    , Biswa Pratim Das Purkayastha1 , Shikha Srivastava1 , Sunanda Chaturvedi2 , Akhtar Ali3 , Dau Dayal Aggarwal1 , Jagat Kumar Roy 4 |
1- Department of Zoology, Banaras Hindu University, Varanasi, India.
2- Homi Bhabha Cancer Hospital & Research Centre, Varanasi, India.
3- Centre for Genetic Disorders, Banaras Hindu University, Varanasi, India.
4- Department of Zoology, Banaras Hindu University, Varanasi, India. , jkroy@bhu.ac.in |
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Abstract: (1337 Views) |
| Among HPV-mediated cervical cancers, cellular factor BRN3A has gained considerable attention due to its role in promoting an anti-apoptotic cellular environment and in facilitating epitheliotropic transformations of the host. The majority of previous studies looked at BRN3A's molecular characteristics; however, the possibility of genetic variations in BRN3A's auto-regulatory region in relation to cervical cancer risk has been underestimated until now. In a retrospective study in the Eastern UP population, India, we detected genetic variations in the cis-regulatory proximal enhancer region located around 5.6 kb upstream of transcription start site of BRN3A. Our analysis of PCR and DNA sequencing confirmed this novel SNP (BRN3A g.60163379A>G) within the auto-regulatory region of BRN3A. As compared to control subjects, cancer cases exhibited a 1.32-fold higher allele frequency (χ2 = 6.315, p = 0.012). In homozygous (GG) but not in heterozygous conditions, odds ratio (OR) analysis suggests a significant association of cancer risk with the SNP (OR = 2.60, p ≤ 0.004). We further confirmed using the functional analysis that this SNP increased the luciferase gene activity in HPV-positive cervical cancer SiHa cells that were exposed to progesterone. As a result of the association of polymorphisms in a non-coding region of an oncogene with increased cancer risks, we are suggesting that this genetic variation in non-coding region can be used in prediction, diagnosis, or predicting the progression of the disease. |
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| Keywords: Cervical cancer, HPV, BRN3A, BRN3A proximal enhancer region, India, g.60163379A>G |
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Full-Text [PDF 911 kb]
(960 Downloads)
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Type of Study: Original Article |
Subject:
Cancer
Received: 2022/01/16 | Accepted: 2022/12/11 | Published: 2022/12/12
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